title: CD8(+) T cell-mediated cytotoxicity toward Schwann cells promotes diabetic peripheral neuropathy.
abstract: BACKGROUND
  Damage to Schwann cells has been reported in the development of diabetic peripheral neuropathy (DPN), but how Schwann cells are damaged has not been elucidated.
  
  
  METHODS
  The highly expressed proteins in the PBMC of DPN patients were identified through MALDI-TOF/TOF and SELDI protein chip technology. The expression levels of CXCR3 were detected by qPCR and flow cytometric analysis. Transwell migration assay was to investigate the migration of CD8(+) T cells. Western-blot analysis was to detect the levels of p38 MAP kinases pathway related proteins and TNF-α, FasL, and PDL1.
  
  
  RESULTS
  Two highly expressed proteins, CXCR3 and p38, were identified. Under high glucose conditions, CXCR3 was elevated in CD8(+) T cells via the activation of p38 MAP kinases. Moreover, CXCL9, CXCL10, and CXCL11 expression were induced in Schwann cells, leading to the recruitment and infiltration of CD8(+) T cells into DPN tissues. Further study demonstrated that Schwann cells promoted activation of CD8(+) T cells and induced expression of TNF-α, FasL, and PDL1 on CD8(+) T cells, in return, CD8(+) T cells induced obvious apoptosis of Schwann cells.
  
  
  CONCLUSIONS
  Our study indicates that CD8(+) T cells mediate cytotoxicity toward Schwann cells and play an important role in the development of DPN.
authors.affiliation: Department of Endocrinology, Shanghai Changzheng Hospital, Shanghai, PR China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Qian
authors.initials: Q
authors.lastname: Lv
authors.forename: Xiang-fang
authors.initials: XF
authors.lastname: Chen
authors.forename: Jun-jie
authors.initials: JJ
authors.lastname: Zou
authors.forename: Zhi-min
authors.initials: ZM
authors.lastname: Liu
authors.forename: Yong-quan
authors.initials: YQ
authors.lastname: Shi
mesh_terms: D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism; D054371:Chemokine CXCL11 / Q000378:metabolism; D054370:Chemokine CXCL9 / Q000378:metabolism; D003929:Diabetic Neuropathies / Q000378:metabolism*; D005434:Flow Cytometry; D005947:Glucose / Q000009:adverse effects; D006801:Humans; D010523:Peripheral Nervous System Diseases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D054367:Receptors, CXCR3 / Q000378:metabolism; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D054367:Receptors, CXCR3; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose